Journal
JOURNAL OF CELL BIOLOGY
Volume 200, Issue 3, Pages 259-270Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201211017
Keywords
-
Categories
Funding
- Institut Curie
- CNRS
- INSERM
- French National Research Agency [08-JCJC-0007]
- HFSP [RGP 23/2008]
- EMBO
- grant NWO-ALW-VICI of the Netherlands Organization for Scientific Research
- Swiss National Science Foundation [310030B_138659]
Ask authors/readers for more resources
Tubulin tyrosine ligase (TTL) catalyzes the post-translational retyrosination of detyrosinated alpha-tubulin. Despite the indispensable role of TTL in cell and organism development, its molecular mechanism of action is poorly understood. By solving crystal structures of TTL in complex with tubulin, we here demonstrate that TTL binds to the alpha and beta subunits of tubulin and recognizes the curved conformation of the dimer. Biochemical and cellular assays revealed that specific tubulin dimer recognition controls the activity of the enzyme, and as a consequence, neuronal development. The TTL-tubulin structure further illustrates how the enzyme binds the functionally crucial C-terminal tail sequence of alpha-tubulin and how this interaction catalyzes the tyrosination reaction. It also reveals how TTL discriminates between alpha- and beta-tubulin, and between different post-translationally modified forms of alpha-tubulin. Together, our data suggest that TTL has specifically evolved to recognize and modify tubulin, thus highlighting a fundamental role of the evolutionary conserved tubulin tyrosination cycle in regulating the nnicrotubule cytoskeleton.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available